Derivatives of hyaluronan

Abstract

The invention describes new hyaluronan derivatives where the hydroxyl groups are esterified or carbamoylated in amounts ranging from 0.01% to 100% and the carboxyl groups are either totally or partially esterified with alcohols or are in the form of salt.

We claim: 
     
       1. Derivatives of hyaluronan, wherein the hydroxyl groups are carbamoylated in amounts ranging from 0.01% to 100% and the carboxyl groups are esterified in amounts of at least 50% with alcohols or they are in the form of salts, wherein the hydroxyl groups are carbamoylated with an isocyanate selected from the group consisting of alkyl isocyanates; alkylaryl isocyanates, and aryl isocyanate; wherein said isocyanate is optionally substituted; wherein said alkyl residue is a linear or branched, saturated or unsaturated C2–C6 alkyl, and wherein the aryl residue is mono- or polynuclear, optionally substituted with a residue selected from the group consisting of linear or branched, saturated or unsaturated C1–C5 alkyls, with halogens, nitro groups, cyano groups, and methoxy groups. 
     
     
       2. Derivatives according to  claim 1 , wherein the hydroxyl groups are carbamoylated with an isocyanate selected from the group consisting of phenylisocyanate, dialkylphenylisocyanate, trialkylphenylisocyanate and 1-phenylethylisocyanate. 
     
     
       3. Derivatives according to  claim 1 , wherein the carboxyl groups are esterified with an alcohol selected from the group consisting of aliphatic, arylaliphatic, aryl, cycloaliphatic, and heterocyclic alcohols. 
     
     
       4. Derivatives according to  claim 1 , wherein the carboxyl group is esterified with an alcohol selected from the group consisting of methylalcohol, benzylalcohol, allylalcohol, and propylalcohol. 
     
     
       5. Derivatives according to  claim 1 , wherein the hydroxyl groups are carbamoylated in amounts ranging from 0.01% to 0.2%. 
     
     
       6. Derivatives according to  claim 1 , wherein the carboxyl groups are totally esterified. 
     
     
       7. Derivatives according to  claim 1 , wherein the carboxyl groups are in the form of salt. 
     
     
       8. Method for the preparation of chromatographic stationary phases comprising providing a solution comprising a derivative of hyaluronan wherein the hydroxyl groups are esterified or carbamoylated in amounts ranging from 0.01% to 100%, the carboxyl groups are esterified in amounts of at least 50% with alcohols or are in the form of salts and their intrinsic viscosity ranges from 0.1 to 22 dl/g and, adding the solution to a chromatographic support. 
     
     
       9. Method according to  claim 8  wherein said stationary phases are chiral stationary phases. 
     
     
       10. Chiral stationary phases comprising derivatives of hyaluronan, wherein the hydroxyl groups are esterified or carbamoylated in amounts ranging from 0.01% to 100%, the carboxylic groups esterified in amounts of at least 50% with alcohols or are in the form of salt; and the intrinsic viscosity of said derivatives ranges from 0.1 to 22 dl/g. 
     
     
       11. Chiral stationary phases according to  claim 10 , wherein the hydroxyl groups of the derivatives of hyaluronan are esterified with an acid selected from the group consisting of inorganic acids; linear or branched, saturated or unsaturated aliphatic acids; cycloaliphatic or aliphatic cycloaliphatic acids optionally polycyclic; arylaliphatic acids; aryl acids; and heterocyclic acids; wherein said acids are optionally substituted with linear or branched C1–C5 alkyl, halogens, hydroxyl groups, amino groups, nitro groups, methoxy groups, and cyano groups. 
     
     
       12. Chiral stationary phases according to  claim 10 , wherein the hydroxyl groups of the derivatives of hyaluronan are carbamoylated with an isocyanate selected from the group consisting of akyl isocyanates; alkylaryl isocyanates, and aryl isocyanates; wherein said isocyanates are optionally substituted with a residue selected from the group consisting of linear or branched C1–C5 alkyls, halogens, nitro groups, cyano groups, and methoxy groups, wherein the alkyl residue is a linear or branched, saturated or unsaturated C2–C6 alkyl and wherein the aryl residue is a mono- or polynuclear residue. 
     
     
       13. Chiral stationary phases according to  claim 10 , wherein the carboxylic groups of the derivatives of hyaluronan are esterified with an alcohol selected from the group consisting of aliphatic, arylaliphatic, aryl, cycloaliphatic, and heterocyclic alcohols. 
     
     
       14. Chiral stationary phases according to  claim 10 , wherein the hydroxyl groups of the derivatives of hyaluronan are esterified or carbamoylated in amounts ranging from 0.01% to 0.2%. 
     
     
       15. Chiral stationary phases according to  claim 14 , wherein the carboxyl groups are totally esterified. 
     
     
       16. Method for the preparation of optically pure isomers or of mixtures of isomers having an enantiomeric content higher than the one in a starting racemic mixture comprising providing a starting racemic mixture; and contacting the racemic mixture with a stationary phase according to  claim 10 . 
     
     
       17. Method for the preparative or analytical separation of enantiomers or mixtures of racemates comprising providing enantiomers or mixtures of racemates and contacting the enantiomers or mixtures of racemates with a stationary phase according to  claim 10 , in the preparative or analytical separation of enantiomers or mixtures of racemates. 
     
     
       18. A chromatographic method comprising contacting enantiomers or mixtures or racemates with a stationary phase according to  claim 10  wherein said chromatographic method is selected from a group consisting of liquid chromatography, High Pressure Liquid Chromatography (HPLC), Simulating Moving Bed Chromatography (SMBC) and Supercritical Fluid Chromotography (SCFC). 
     
     
       19. Chiral stationary phases according to  claim 10 , where in the hydroxyl groups of the derivatives of hyaluronan are esterified or carbamoylated in amounts ranging from 70% to 100%. 
     
     
       20. Chiral stationary phases according to  claim 19 , wherein the carboxyl groups are either totally esterified or are in the form of salt.